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Background  Pathogens tolerate stress conditions that include low pH, oxidative stress, high salt and high temperature in order to survive inside and outside their hosts. Lipopolysaccharide (LPS), which forms the outer-leaflet of the outer membrane in Gram-negative bacteria, acts as a permeability barrier. The lipid A moiety of LPS anchors it to the outer membrane bilayer. The MsbB enzyme myristoylates the lipid A precursor and loss of this enzyme, in  Salmonella , is correlated with reduced virulence and severe growth defects that can both be compensated with extragenic suppressor mutations.    Results  We report here that  msbB  (or  msbB somA )  Salmonella  are highly sensitive to physiological CO 2  (5%), resulting in a 3-log reduction in plating efficiency. Under these conditions,  msbB Salmonella  form long filaments, bulge and lyse. These bacteria are also sensitive to acidic pH and high osmolarity. Although CO 2  acidifies LB broth media, buffering LB to pH 7.5 did not restore growth of  msbB  mutants in CO 2 , indicating that the CO 2 -induced growth defects are not due to the effect of CO 2  on the pH of the media. A transposon insertion in the glucose metabolism gene  zwf  compensates for the CO 2  sensitivity of  msbB Salmonella . The  msbB zwf  mutants grow on agar, or in broth, in the presence of 5% CO 2 . In addition,  msbB zwf  strains show improved growth in low pH or high osmolarity media compared to the single  msbB  mutant.    Conclusion  These results demonstrate that  msbB  confers acute sensitivity to CO 2 , acidic pH, and high osmolarity. Disruption of  zwf  in  msbB  mutants restores growth in 5% CO 2  and results in improved growth in acidic media or in media with high osmolarity. These results add to a growing list of phenotypes caused by  msbB  and mutations that suppress specific growth defects.

msbB deletion confers acute sensitivity to CO2 in Salmonella enterica serovar Typhimurium that can be suppressed by a loss-of-function mutation in zwf